1. Field of the Invention
The present invention relates to a multilayer chemical analytical element employable for analysis of a biological fluid. More particularly, the invention relates to a multilayer chemical analytical element free from interference (disturbance) with quantitative analysis of analyte contained in a blood sample (i.e., whole blood, plasma or serum) which is caused by a fluoride contained in the blood sample as preservative.
2. Description of Prior Arts
It is widely employed that a fluoride such as sodium fluoride or lithium fluoride is incorporated into a blood sample (the blood sample means to include whole blood, plasma, and serum, unless otherwise specified in the specification) as a preservative. Since the fluoride serves for preventing glycolysis, in addition to serving as preservative for preventing blood coagulation, the fluoride is appropriately incorporated into a blood sample for measurement of glucose content. See, Handbook of Clinical Tests, 29th revision, originally written by Izumi Kanai, and edited by Masamitsu Kanai (Kanahara Shuppan, Japan, 1983) page 228; and R. D. Henry, D. C. Cannon, J. W. Winkelman, Clinical Chemistry Principles and Technics, 2nd edition (Harper & Row. Publishers, 1974), pages 385-388, etc.
The fluoride (preservative) is incorporated into a blood sample generally by adding the fluoride to the blood just after collection the blood, or collecting a blood into a blood-collecting tube having a fluoride on the inner surface thereof. The fluoride is generally incorporated into a blood sample in an amount of approx. 1 mg. to approx. 10 mg. per 1 ml. in the case that the fluoride is NaF. It has been found that the flourine anion brings about interference effect (disturbance effect) on an analyte to give a lower value (minus error) in analyses using anzymes, particularly an oxidase (e.g., glucose oxidase, cholesterol oxidase, etc.) which are very widely employed at present. Particularly, in the case of analysis of a blood sample containing a great amount of a fluoride as well as in the case of analysis of a blood sample containing a fluoride using a multilayer analytical element through the so-called dry analysis, the minus error caused by the presence of a fluoride anion increases. Therefore, the minus error mentioned above should be solved in the art.
Japanese Patent Publication No. 57(1982)-28277 describes that the minus error observed in the use of an integral multilayer analytical element for quantitative determination of glucose can be avoided by incorporating a pH-adjusting buffer or an organic acid capable of maintaining the surrounding conditions at pH 5.0-5.6 during development of the analysis such as 3,3-dimethylglutaric acid, succinic acid or malic acid into a reagent layer containing a composition for measurement of glucose which comprises glucose oxidase, peroxidase, 4-aminoantipyrine and 7-hydroxy-1-naphthol.
Japanese Patent Application No. 57(1982)-131750 (EP No. 101 945 A1, published on Mar. 7, 1984) describes that the minus error caused by the presence of a fluoride in the use of a multilayer analytical element can be avoided by employing calcium acetate or the like containing calcium cation capable of forming a sparingly water soluble salt with the fluorine anion in conjunction with the composition for glucose or cholresterol analysis which comprises an oxidase such as glucose oxidase or cholesterol oxidase, peroxidase, 4-aminoantipyrine and 1,7-dihydroxynaphthalene.
It has been now discovered by the present inventors that the incorporation of light-blocking layer or light-reflecting layer utilizing the conventionally employed titanium dioxide fine powder provided on the surface with aluminum oxide, silicon oxide, there analogues or a combination thereof into a multilayer analytical element for quantitative measurement of glucose employing the abovedescribed improved technology is still apt to give a minus error in the presence of a fluoride. Moreover, it has been discovered that the multilayer analytical element for quantitative measurement of glucose employing the calcium acetate gives a plus error in the presence of a small amount of a fluoride, while the element gives a minus error in the presence of a large amount of a fluoride. Thus, in the latter case, the fluoride brings about complicated interference effect (disturbance effect) in the analytical element.